MAGNETIC SPHINCTER AUGMENTATION DEVICE FOR GASTROESOPHAGEAL REFLUX DISEASE: EFFECTIVE, BUT POSTOPERATIVE DYSPHAGIA AND RISK OF EROSION SHOULD NOT BE UNDERESTIMATED. A SYSTEMATIC REVIEW AND META-ANALYSIS

ABSTRACT BACKGROUND: Magnetic ring (MSA) implantation in the esophagus is an alternative surgical procedure to fundoplication for the treatment of gastroesophageal reflux disease. AIMS: The aim of this study was to analyse the effectiveness and safety of magnetic sphincter augmentation (MSA) in patients with gastroesophageal reflux disease (GERD). METHODS: A systematic literature review of articles on MSA was performed using the Medical Literature Analysis and Retrieval System Online (Medline) database between 2008 and 2021, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A random-effect model was used to generate a pooled proportion with 95% confidence interval (CI) across all studies. RESULTS: A total of 22 studies comprising 4,663 patients with MSA were analysed. Mean follow-up was 27.3 (7–108) months. The weighted pooled proportion of symptom improvement and patient satisfaction were 93% (95%CI 83–98%) and 85% (95%CI 78–90%), respectively. The mean DeMeester score (pre-MSA: 34.6 vs. post-MSA: 8.9, p=0.03) and GERD-HRQL score (pre-MSA: 25.8 vs. post-MSA: 4.4, p<0.0001) improved significantly after MSA. The proportion of patients taking proton pump inhibitor (PPIs) decreased from 92.8 to 12.4% (p<0.0001). The weighted pooled proportions of dysphagia, endoscopic dilatation and gas-related symptoms were 18, 13, and 3%, respectively. Esophageal erosion occurred in 1% of patients, but its risk significantly increased for every year of MSA use (odds ratio — OR 1.40, 95%CI 1.11–1.77, p=0.004). Device removal was needed in 4% of patients. CONCLUSIONS: Although MSA is a very effective treatment modality for GERD, postoperative dysphagia is common and the risk of esophageal erosion increases over time. Further studies are needed to determine the long-term safety of MSA placement in patients with GERD.


A QUEDA DA PRESSÃO PORTAL APÓS DESVASCULARIZAÇÃO ESOFAGOGÁSTRICA E ESPLENECTOMIA INFLUENCIA A VARIAÇÃO DO CALIBRE DAS VARIZES E AS TAXAS DE RESSANGRAMENTO NA ESQUISTOSSOMOSE NO SEGUIMENTO EM LONGO PRAZO?
Does the drop in portal pressure after esophagogastric devascularization and splenectomy variation of variceal calibers and the rebleeding rates in schistosomiasis in late follow-up?
Walter de Biase SILVA-NETO 1 , Claudemiro QUIRESE 1 , Eduardo Guimarães Horneaux de MOURA 2 , Fabricio Ferreira COELHO 3 , Paulo HERMAN 3 ABSTRACT -Background: The treatment of choice for patients with schistosomiasis with previous episode of varices is bleeding esophagogastric devascularization and splenectomy (EGDS) in association with postoperative endoscopic therapy.However, studies have shown varices recurrence especially after long-term follow-up.Aim: To assess the impact on behavior of esophageal varices and bleeding recurrence after post-operative endoscopic treatment of patients submitted to EGDS.Methods: Thirty-six patients submitted to EGDS portal pressure drop, more or less than 30%, and compared with the behavior of esophageal varices and the rate of bleeding recurrence.Results late post-operative varices caliber when compared the pre-operative data was observed despite an increase in diameter during follow-up that was controlled by endoscopic therapy.

Perspectives
The magnetic sphincter augmentation device is an effective treatment modality for GERD.Most patients undergoing MSA placement achieve symptom relief and improvement in quality of life.Postoperative dysphagia is common after the procedure.Although esophageal erosion is rare, its risk increases significantly over time.Further studies with objective assessment of results and longer follow-up are still needed.

Central Message
Gastroesophageal reflux disease (GERD) significantly impairs quality of life and work productivity.It also represents a substantial financial burden to the health-care system.Dietary and lifestyle modifications along with antireflux medication are recommended for the treatment for GERD.The laparoscopic fundoplication has been the most common surgical procedure to treat GERD in the last decades; however, in 2008, a novel laparoscopically implantable magnetic sphincter augmentation (MSA) device was described, which was designed to restore the lower esophageal sphincter barrier function.Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.Medical Literature Analysis and Retrieval System Online (Medline) and Cochrane Central Register of Controlled Trials databases were systematically searched for all articles published from January 2008 to February 2021.The following medical subject headings were used to identify relevant studies: "magnetic sphincter augmentation", "LINX", "Magnetic sphincter augmentation and gastroesophageal reflux disease", "Magnetic sphincter augmentation for GERD".The keywords were used in all possible combinations to obtain the maximal number of articles.The reference list of the retrieved articles was also screened to find articles that were missed during the primary search.

Selection criteria and data extraction
All studies reporting outcomes of patients who underwent MSA device implantation were included in the analysis.The search was limited to articles in English.Experimental studies in animal models, abstracts, case reports, reviews, editorials, and comments were excluded.
A total of 617 articles were initially screened; after removing duplicates and excluding titles and abstracts that did not meet the inclusion criteria, 52 articles were revised by two independent authors (ACV and CAA) based on the methodological quality of the publications.Discrepancies between the two reviewers were resolved by discussion and consensus with the senior author (FS).Finally, 22 articles were included for the metaanalysis  (Table 1 and 2). The ivestigators (ACV, CAA) independently evaluated and extracted the data from all the eligible publications.The following data were extracted from the articles: author, publication year, design, population size, gender, age, body mass index (BMI), follow-up, preoperative GERD Health-Related Quality of Life (GERD-HRQL) score, preoperative use of proton pump inhibitor (PPI), preoperative DeMeester score, operative time, 30-day overall morbidity, 30-day mortality, length of hospital stay (LOS), symptoms improvement, satisfaction rates, postoperative GERD-HRQL score, postoperative use of PPI, postoperative DeMeester score, dysphagia, endoscopic dilation, gas-related symptoms, erosion, and device removal rates.

Endpoints
The primary endpoint was effectiveness, which was assessed by symptom improvement, GERD-HRQL score, satisfaction rates, postoperative DeMeester score, and postprocedural use of PPIs.Secondary endpoints included: postoperative dysphagia, need for endoscopic dilation, gas-related symptoms, esophageal erosion, and device removal rates (Figure 2).

Statistical analysis
The summary statistics were treated as independent observations and analyzed using standard methods for independent data.A meta-analysis of proportions was conducted for the following variables: symptom improvement, satisfaction, dysphagia, endoscopic dilatation, gas-related symptoms, esophageal erosion, and device removal.Statistical heterogeneity was assessed with the I2 statistic, and significance was assumed when the I2 was greater than 50%.Heterogeneity was also defined as a Cochran Q <0.10.As there was evidence of significant heterogeneity across studies, a random-effect model (DerSimonian-Laird method) was used to generate a pooled proportion with 95% confidence interval (CI) across all studies.
Average proportion of patients using PPI, DeMeester Score, and GERD-HRQL score before and after treatment were compared using a paired two-sample t-test.Logistic regression was used to model the effect of the procedure on esophageal erosion while adjusting for length of follow-up.The statistical analysis was performed using R (version 4.0.4) and R Studio INTRODUCTION G astroesophageal reflux disease (GERD) is a condition which develops when the reflux of stomach contents into the esophagus causes troublesome symptoms or complications 53 .GERD is the most prevalent gastrointestinal disorder across the United States, ranging from 6 to 30%, with approximately 110 thousand hospital admissions annually 2,21,51 .Current evidence suggests that its incidence is increasing, mainly due to the rising prevalence of obesity worldwide 35 .As GERD significantly impairs quality of life and work productivity, it also represents a substantial financial burden to the health-care system 27 .
Dietary and lifestyle modifications along with antireflux medication (i.e.proton pump inhibitors [PPI]) are the mainstay of treatment for GERD.However, it is estimated that up to 40% of patients fail to respond to medical therapy 15,22,30,32,36 .The Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) guidelines on the management of GERD recommend that surgical treatment be considered in individuals who have failed medical therapy, have GERD complications, and/or present extra-esophageal manifestations 39 .
The laparoscopic fundoplication has been the most common surgical procedure to treat GERD in the last decades 2,24,37 .
In 2008, a multicenter study described a novel laparoscopically implantable magnetic sphincter augmentation (MSA) device designed to restore the lower esophageal sphincter barrier function 13 .It consists in multiple adjustable beads that are placed around the gastroesophageal junction.The magnetic union between each of the beads allows the passage of the swallowed bolus but inhibits the reflux of stomach contents into the esophagus 5 (Figure 1).Although several studies have demonstrated the safety and efficacy of the device 3-5,7,10- 14,16,19,20,23,25,26,29,32-34,40,41,43,45,46,48-50,52,55 , large series and randomized trials supporting its use are still lacking.
The aim of this systematic review and meta-analysis was to summarize all the currently available evidence on MSA to determine its safety and effectiveness for GERD treatment.

Search strategy
A systematic literature review of articles on laparoscopic MSA device placement was performed according to the Preferred

RESULTS
A total of 22 studies comprising 4,663 patients with MSA device were included in the analysis.Mean age was 52.6 (39.3-64.3)years, 53% were males, and mean BMI was 27.2 (23.9-29.8)kg/m 2 .Mean operative time was 62.4 (43.2-81) minutes; 30-day overall morbidity rate was 0.7% and no mortality was reported.Mean LOS was 28.2 (5.2-53) hours.Mean follow-up across the studies was 27.3 (7-108) months.Table 1 and 2 describes the main characteristic of the studies included in the analysis.

Figure -
The proportion forest plot of endoscopic dilation.
. The weighted pooled proportion of esophageal erosion was 1% (95%CI 0-2%).The heterogeneity chi-squared was 1.05 (p<0.04) with an I2 statistic of 50%.Follow-up time was found to be significantly associated with the odds of esophageal erosion.It was estimated that the odds of erosion increased by a factor of 1.40 per every year increase in follow-up time (odds ratio -OR 1.40, 95%CI 1.11-1.77,p=0.004).The weighted pooled proportion of patients with device removal was 4% (95%CI 3-6%).The heterogeneity ꭓ 2 was 0.31 (p<0.01) with an I2 statistic of 69%.

DISCUSSION
We aimed to determine the effectiveness and safety of the MSA device placement in patients with GERD.
We found that: a) the MSA device is very effective as most patients obtain symptom relief and quality of life improvement; b) postoperative dysphagia and need for endoscopic dilation are relatively common; and c) the risk of esophageal erosion is low but increases significantly over time.
The MSA procedure is currently approved for GERD patients with indication for antireflux surgery, normal esophageal motility, BMI <35 kg/m 2 , no previous foregut surgery, and hiatal hernia <3 cm 38 .Despite these restricted indications, several studies have determined the effectiveness of the procedure.The pivotal trial, a multi-center study including 100 patients, reported a 90% reduction of GERD symptoms with 86% of patients without PPI use at two years of followup 3,4,7,10,11,14,16,19,20,23,25,26,34,40,41,43,45,48,50,52,55 .Similarly, a recent study including 553 patients showed that 84% of patients had at least 50% improvement in the GERD-HRQL score at a median follow-up of 10.6 months.Although our pooled analysis had a relatively short mean follow-up (27.3 months), our findings confirmed that most patients undergoing MSA implantation achieve a substantial improvement in GERD symptoms (93%) and are satisfied with the results (85%).Unfortunately, few studies showed objective data for assessment of postoperative results.DeMeester scores, however, significantly decreased in those studied with pH monitoring.In addition, few patients required PPIs after MSA implantation (12.4 %).
Dysphagia is a possible side effect of the procedure and represents one of the main indications for the MSA device removal.A previous study reported a dysphagia rate of 15.5% among 380 patients undergoing MSA placement with an overall response to the endoscopic dilatation of 68%.Only 1.8% of patients with dysphagia required device removal 6 .Another study found that the most common reason for removal was symptom recurrence (46%), followed by dysphagia (37%), and chest pain (18%) 5 .Our pooled analysis confirmed that the MSA procedure is associated with a relatively high incidence of postoperative dysphagia (18%), and a non-negligible proportion of patients (13%) required at least one endoscopic dilation.
Esophageal erosion and perforation are the main concerns after MSA device placement.In fact, "similar" type of devices such as the Angelchick prosthesis for GERD and the adjustable gastric band for obesity have been associated with these serious complications 6,54 .Salvador et al. reported two cases of severe dysphagia after MSA procedure due to migration of the device into the esophagus.The devices were safely removed endoscopically in a single step in both cases 47 .In agreement, Bona et al. concluded in 2021 that MSA devices can be safely explanted via a single-stage laparoscopic procedure associated with common antireflux procedures 9 .However, the MSA device has proven to be safe among most published studies [3][4][5]7,[10][11][12][13][14]16,19,20,23,25,26,29,[32][33][34]40,41,43,45,46,[48][49][50]52,55 . For instance, a recent study that analyzed the manufacturer'sdatabase reported 29 cases of erosions among 9,453 devices placed (0.3%) over four years of follow-up.Median time to erosion was 26 months, and endoscopic removal of the device was also feasible in the majority of cases 1 .The risk of erosion has been linked to the number of beads (smaller devices with small number of beads fit tightly around the esophagus).Bologheanu et al. observed that the presence of fewer than 13 beads was an independent risk factor for developing postoperative dysphagia 8 .For that reason, the MSA device with 12 beads was recently removed from the market.Our pooled analysis showed low rates of erosion (1%) and device removal (4%).Nevertheless, we found that the risk of erosion increased significantly for every year of MSA device use (OR 1.40).Therefore, considering the short follow-up of most studies, the risk of esophageal erosion should not be underestimated yet.
The Nissen fundoplication is still the mainstay of surgical treatment for GERD.Interestingly, a recent meta-analysis comparing MSA with fundoplication concluded that there were no significant differences between the procedures in terms of PPIs usage, GERD-HRQL score, dysphagia, and reoperation rates 28 .Another matched pair analysis showed that patients undergoing MSA procedure achieved similar symptom control with less gas-related symptoms, and greater ability to belch 42 .Other potential advantages of laparoscopic placement of MSA device include that it is less technically demanding, requires minimal dissection of the gastric fundus, and has no permanent anatomical alterations 31 .On the other hand, opposite to MSA procedure, the fundoplication has been used for more than 65 years and has already proven excellent longterm effectiveness 17,38,44 .High expenses and lack of coverage by many insurance companies are also drawbacks of the MSA device that should be considered.
This study has several limitations.First, several methodological design discrepancies were noted among the analyzed studies.Second, most studies included in the analysis had a short followup.Third, statistical heterogeneity was relevant in many of the assessed outcomes.Finally, few studies evaluated patients with postoperative pH monitoring.Future studies should include standardized diagnostic methods to allow objective and comparable assessment of outcomes.

CONCLUSIONS
The MSA device is an effective treatment modality for GERD.Most patients undergoing MSA placement achieve symptom relief and improvement in quality of life.Postoperative dysphagia is common after the procedure.Although esophageal erosion is rare, its risk increases significantly over time.Further studies with objective assessment of results and longer follow-up are still needed.

Figure 1 -
Figure 1 -Location of the magnetic sphincter augmentation device.

Figure 1 - 8 ABCD
Figure 1 -Schematic representation of the magnetic sphincter augmentation device placed around the gastroesophageal junction.

Figure 2 -
Figure 2 -Analysis of the articles performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA).

Figure 3 - 8 ABCD
Figure 3 -The proportion forest plot of symptom improvement.

Figure -
Figure -The proportion of patient satisfaction.

Figure -
Figure -The proportion forest plot of postoperative dysphagia.

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MAGNETIC SPHINCTER AUGMENTATION DEVICE FOR GASTROESOPHAGEAL REFLUX DISEASE: EFFECTIVE, BUT POSTOPERATIVE DYSPHAGIA AND RISK OF EROSION SHOULD NOT BE UNDERESTIMATED.A SYSTEMATIC REVIEW AND META-ANALYSIS 5Arq Bras Cir Dig 2023;36:e1781

Table 1 -
Characteristics of studies included in the meta-analysis pre-magnetic sphincter augmentation.

Table 2 -
Characteristics of studies included in the meta-analysis post-magnetic sphincter augmentation.Version 1.4.1106)software.A p<0.05 was considered statistically significant in all the analyses.The study was approved by the Ethics Committee of the Institution (nº 2342346).